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Title: Cardiovascular effects of oral contraceptives: a review.
Author: Stubblefield PG.
Journal: Int J Fertil; 1989; 34 Suppl():40-9. PubMed ID: 2576258.
Abstract:
The evidence for and against the association of oral contraceptives (OCs) with vascular disease is reviewed, along with the possible pathophysiologic mechanisms for such an association, including effects on coagulation, circulating lipoproteins, and glucose metabolism. The new, low-dose estrogen OCs appear to affect coagulation minimally, and anticoagulant as well as procoagulant effects have been documented. Such concomitant factors as cigarette smoking, obesity, a family history of thrombosis, lack of physical activity, and blood type influence coagulation more strongly. Myocardial infarction and stroke are strongly correlated with the levels and pattern of circulating lipoproteins. The estrogen components of OCs have a favorable effect on lipids, while the effect of progestins, particularly potent androgenic progestins, is unfavorable and could be significant. OCs containing high-dose androgenic progestins can produce abnormal glucose tolerance resulting in increased cardiovascular risk. Low-dose OCs are associated with early, transient breakthrough bleeding. However, educating patients in the management of breakthrough bleeding can help reduce the number of women who must be switched to higher-dose OCs. Epidemiologic evidence confirms the safety of low-dose OCs. By selecting patients carefully, the risk of vascular disease from oral contraception can be reduced to very low levels. In this review of cardiovascular effects of oral contraceptives (OCs), the risks are identified from 2 prospective cohort studies as 19/10,000 woman years for the risk of thrombosis or thromboembolism. 11 of 19 were superficial thrombosis and 8 were deep vein thrombosis or pulmonary embolism. For women with no risk factors, the risk was 2.0 for superficial thrombosis and 4.0 for deep vein thrombosis. Myocardial infarction (MI) risk is estimated at 7/100,000 current users/year for women 30-39 years and 67/100,000/year for women 40-44 years based on combined British and American studies. 37/100,000/year is the estimated risk for women 30-44 years for either thrombotic or hemorrhagic stroke. 50% of the MIs and 10% of the strokes were fatal. The total annual risk of death from any circulatory disease was estimated at 22-24 deaths/100,000 women years based on 2 British cohort studies. Other predisposing factors also contribute to cardiovascular disease, and separating out the effects has been controversial. In 1985, a study refuted that OCs were responsible for any effect on cardiovascular risk, because of flawed case control studies. One such study is cited which shows that only 16.7% of OC users were confirmed by Doppler ultrasound for deep vein thrombosis compared with 30.7% for nonusers. The general trend in the UK is one of reduced death rates from circulatory disease for women in spite of widespread contraceptive use. This relationship between OC use and cardiovascular disease was evidenced in another study of vital statistics from 21 countries. The pathological mechanisms for the association between OC use and vascular disease are discussed for blood clotting with the importance of predisposing factors highlighted, MI and lipid metabolism and other risk factors, stroke, and breakthrough bleeding. The risk is very low for vascular disease with available low- dose preparations. Risk is further reduced with careful screening of high risk women. The side effects of low-dose pills such as breakthrough bleeding can be treated with cautious use of alternative high-dose formulations and patient education. Low-dose OCs with 30-35 mg of estrogen combined with a low-dose and low androgenic progestin are recommended.

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